1. Intracerebral cannulas were implanted stereotactically into the nucleus accumbens, dorsal striatum or nucleus entopeduncularis of male NMRI mice. 2. Monoamine-depleted mice were injected intracerebrally with the competitive NMDA receptor antagonist AP-5, the non-competitive NMDA antagonist MK-801 or the AMPA-kainate receptor antagonist CNQX. A marked locomotor stimulation was produced when AP-5 was injected into the nucleus accumbens, but not when injected into the dorsal striatum. Likewise, CNQX stimulated locomotor activity when injected into the nucleus accumbens. Neither AP-5 nor CNQX produced behavioral stimulation following injection into the nucleus entopeduncularis. 3. The tone in the monoaminergic systems influences the potency of competitive and non-competitive NMDA antagonists differently with regard to stimulation of locomotor activity. In the case of the competitive NMDA antagonist AP-5 the potency was higher in monoamine-depleted than in monoaminergically intact mice. In contrast, the potency of the non-competitive NMDA antagonist MK-801 was higher in monoaminergically intact than in monoamine-depleted animals. 4. A unilateral injection of AP-5 into the nucleus accumbens caused the animals to rotate: The rotation was predominantly ipsilateral in monoaminergically intact animals, whereas monoamine-depleted mice rotated exclusively contralaterally. When AP-5 was given to monoamine-depleted mice treated with the D-2 agonist quinpirole the animals rotated ipsilaterally, whereas monoamine-depleted mice treated with the D-1 agonist SKF 38393 still rotated contralaterally after AP-5 treatment. These data show that glutamatergic neurons projecting to the nucleus accumbens can affect behavior in different directions depending on the degree of dopamine D-2 receptor stimulation.